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891.
Guo W Lasky JL Chang CJ Mosessian S Lewis X Xiao Y Yeh JE Chen JY Iruela-Arispe ML Varella-Garcia M Wu H 《Nature》2008,453(7194):529-533
Cancer stem cells, which share many common properties and regulatory machineries with normal stem cells, have recently been proposed to be responsible for tumorigenesis and to contribute to cancer resistance. The main challenges in cancer biology are to identify cancer stem cells and to define the molecular events required for transforming normal cells to cancer stem cells. Here we show that Pten deletion in mouse haematopoietic stem cells leads to a myeloproliferative disorder, followed by acute T-lymphoblastic leukaemia (T-ALL). Self-renewable leukaemia stem cells (LSCs) are enriched in the c-Kit(mid)CD3(+)Lin(-) compartment, where unphosphorylated beta-catenin is significantly increased. Conditional ablation of one allele of the beta-catenin gene substantially decreases the incidence and delays the occurrence of T-ALL caused by Pten loss, indicating that activation of the beta-catenin pathway may contribute to the formation or expansion of the LSC population. Moreover, a recurring chromosomal translocation, T(14;15), results in aberrant overexpression of the c-myc oncogene in c-Kit(mid)CD3(+)Lin(-) LSCs and CD3(+) leukaemic blasts, recapitulating a subset of human T-ALL. No alterations in Notch1 signalling are detected in this model, suggesting that Pten inactivation and c-myc overexpression may substitute functionally for Notch1 abnormalities, leading to T-ALL development. Our study indicates that multiple genetic or molecular alterations contribute cooperatively to LSC transformation. 相似文献
892.
基于电功图的抽油机井工况诊断模型 总被引:1,自引:0,他引:1
针对目前缺乏典型工况特征的电功图图集而导致电功图资料无法被充分应用、采油生产系统实时工况诊断难等问题,考虑曲柄实际角速度、四连杆的惯性、摩擦等因素,推导基于光杆示功图的电功图计算模型,建立13种油井工况下的典型电功图特征图集和基于特征值的电功图工况诊断模型,并编制工况诊断软件。经现场5口油井功图计算检验,结果表明:实测电功图与计算电功图的上、下冲程功率峰值、功率的极差、平均功率的平均相对误差分别为1.74%、3.89%、2.96%、1.74%。经现场6口油井电功图的工况诊断检验,该井下工况诊断结果与示功图诊断结果一致,表明基于电功图的抽油机井工况诊断模型准确率高,能为抽油机井采油系统智能分析和优化决策提供技术支持。 相似文献
893.
K Shimizu D Birnbaum M A Ruley O Fasano Y Suard L Edlund E Taparowsky M Goldfarb M Wigler 《Nature》1983,304(5926):497-500
The homologue of the viral Kirsten ras (v-Ki-ras) gene found in the human lung carcinoma cell line, Calu-1, has an intron-exon structure similar to that of the human homologue of the viral Harvey ras (v-Ha-ras) gene. A second, potential fourth coding exon is present in the human Ki-ras gene and similar sequences are found in the Kirsten murine sarcoma virus. Cysteine is encoded at the twelfth amino acid position, suggesting that the Calu-1 Ki-ras gene has undergone a mutational activation at the same position as the human Ha-ras gene of the bladder carcinoma cell line, T24. A comparison of their predicted amino acid sequences suggests that ras proteins have a 'constant' region and a 'variable' region. Here we propose a common modular structure for ras gene products in which the variable region forms a physiologically important combining site. 相似文献
894.
In sympathetic ganglia of the bullfrog, a slow synaptic potential lasting for minutes--the late slow excitatory postsynaptic potential (e.p.s.p.)--was discovered. This slow response, unlike other previously known synaptic potentials in the autonomic nervous system, is not mediated by acetylcholine or monoamines. Similar non-cholinergic, non-adrenergic slow synaptic potentials have since been found in several other vertebrate autonomic ganglia. We found that the late slow e.p.s.p. is probably mediated by a peptide that is identical to, or closely resembles, mammalian luteinizing hormone releasing hormone (LHRH), because (1) when applied directly to sympathetic neurones, LHRH and its agonists elicit a slow depolarization, associated with similar changes in membrane conductance and excitability as those occurring during the late slow e.p.s.p. Furthermore, both peptide-induced and nerve-evoked responses are blocked by antagonists of LHRH; and (2) radioimmunoassays indicate that a chain of sympathetic ganglia contains 100-800 pg of a LHRH-like peptide. Its distribution among spinal nerves, the great reduction of this substance following denervation, and its release from ganglia following isotonic KCl treatment or nerve stimulation suggest that the LHRH-like material is contained in preganglionic nerve fibres. Here we report that immunohistochemical staining of sympathetic ganglia shows that LHRH-like immunoreactivity is indeed present in synaptic boutons. We also show that the two types of ganglion cells (B cells and C cells) receive strikingly different patterns of peptidergic innervation. 相似文献
895.
Ultrastructural correlation of water reabsorption in isolated rat cauda epididymidis 总被引:2,自引:0,他引:2
Electron microscopic study was made on the water reabsorption of the epithelial cells of the rat cauda epididymidis. It was shown that when the epididymal duct was reabsorbing water at a maximal rate, widely dilated intercellular spaces were seen. It is suggested that the standing gradient model of water reabsorption first proposed for the gall bladder may also operate in the cauda epididymidis. 相似文献
896.
K. Bessho S. Yamada T. Kunitani T. Nakamura T. Hashiguchi Y. Tanimoto S. Harada H. Yamamoto R. Hosono 《Cellular and molecular life sciences : CMLS》1995,51(3):284-288
Here we describe a device for testing possible influences of high magnetic fields on biological processes, by which alternating-current magnetic stimuli as high as 1.7 T can be administered. Experiments with a simple multicellular organism, the nematodeCaenorhabditis elegans, revealed that intermittent exposure to the magnetic fields modestly inhibited the animal's reproduction as well as its post-embryonic development, and caused a marked but transient derangement in its locomotory behavior. Available evidence indicates that alternating high magnetic fields can elicit both chronic and acute biological effects, but that the effects may be well tolerated or compensated for by the living organism. 相似文献
897.
混凝土的蠕变断裂试验是一个相当困难的试验,以前还没有人成功地做过这样的试验。我们利用预裂的办法尽量减少混凝土的离散性进行了蠕变断裂试验,获得了蠕变断裂时间和荷载比关系,充分证实了篇变断裂的存在,以及发现在篇变断裂过程中伴随有微裂纹扩展。目前,我们用粘弹性理论蠕变断裂现象进行了初步分析,计算成果和试验非常好地呈现一致性。 相似文献
898.
Jeng JH Wang YJ Chang WH Wu HL Li CH Uang BJ Kang JJ Lee JJ Hahn LJ Lin BR Chang MC 《Cellular and molecular life sciences : CMLS》2004,61(1):83-96
Betel quid (BQ) chewing shows a strong correlation to the incidence of oral submucous fibrosis (OSF), leukoplakia and oral cancer. BQ contains mainly areca nut, lime, Piper betle leaf (PBL) and the inflorescence of P. betle (IPB). Hydroxychavicol (4-allyl-catechol, HC), as a major phenolic compound in PBL and IPB, is shown to induce oxidative stress, glutathione (GSH) depletion and cell cycle deregulation. Using bivariate BrdU/PI flow cytometry, KB cells in DNA synthesis (S phase) are shown to be sensitive to the toxic effect of HC and show cell cycle arrest and apoptosis following exposure to 0.1 and 0.3 mM HC. HC-induced apoptosis and cell cycle arrest are associated with mitochondrial membrane potential (m) depolarization as revealed by a decrease in rhodamine fluorescence. N-acetyl-L-cysteine (1 mM), superoxide dismutase (100 U/ml) and catalase (1000 U/ml) were effective in prevention of HC-induced GSH depletion (as indicated by chloromethylfluorescein fluorescence), reactive oxygen species (ROS) production (by dichlorofluorescein fluorescence), cell cycle arrest and apoptosis. However, dimethylthiourea (2 mM), neocuproine (1 mM), 1,10-phenanthroline (200 M) and desferrioxamine (0.5 mM) showed little effect on HC-induced cell changes. HC elevated the cellular and mitochondrial GSH levels at moderate concentrations (0.05–0.1 mM), whereas at a concentration of 0.3 mM, inhibitory effects were noted. These results indicate that HC consumption may be associated with BQ-chewing-related oral mucosal diseases via GSH depletion, ROS production, mitochondrial dysfunction, cell cycle disturbance and the induction of apoptosis. These events are related to the production of superoxide radicals and hydrogen peroxide.Received 9 July 2003; received after revision 28 September 2003; accepted 24 October 2003 相似文献
899.
在一定电场强度陡脉冲的作用下,细胞膜会形成大量微孔,其数量和孔径会随电场强度的增加而激增,从而引起膜组织断裂,导致细胞死亡,这种现象被称为不可逆性电击穿,为了研究陡脉冲对肿瘤细胞的不可逆性电击穿,应用现代电力电子技术和高电压新技术,研制出了一套脉冲峰值、脉冲宽度、脉冲重复频率和脉冲陡度独立可调的能量可控陡脉冲肿瘤治疗仪。分析了该治疗仪各部分电路的工作原理,在实验室调试成功的基础上,应用该仪器对人卵巢腺癌SKOV3细胞进行了细胞实验,调试时的示波器实测波形和细胞实验的电镜结果表明,该治疗仪性能稳定,能够方便地调节输出脉冲的能量,能有效地杀伤肿瘤细胞。 相似文献
900.
This paper presents an experimental research aiming to realize an artificial hind wing that can mimic the wing unfolding motion of AIIomyrina dichotoma, an insect in coleopteran order. Based on the understanding of working principles of beetle wing folding/unfolding mechanisms, the hind wing unfolding motion is mimicked by a combination of creative ideas and state-of-art artificial muscle actuator. In this work, we devise two types of artificial wings and the successfully demonstrate that they can be unfolded by actuation of shape memory alloy wires to provide actuation force at the wing base and along the leading edge vein. The folding/unfolding mechanisms may provide an insight for portable nano/micro air vehicles with morphing wings. 相似文献